The Association of qSOFA, SOFA, and SIRS with Mortality in Emergency Department Pneumonia

Objective: To determine the association between 30-day mortality with Systemic Inflammatory Response Syndrome (SIRS), Sequential Organ Failure Assessment (SOFA), and quick SOFA (qSOFA) in emergency department patients with pneumonia. Secondary outcomes included the association of sepsis scores with hospital admission and direct ICU admission. Methods: This is a secondary analysis of a pneumonia population conducted in the emergency department of 3 tertiary care medical centers and 4 community hospitals. Adult immunocompetent patients diagnosed with pneumonia were included from 3 twelve-month periods spanning December 2009 to October 2015. We generated area under the receiver operating characteristic curve (AUC) values for each sepsis score for our primary outcome of 30-day mortality and secondarily for hospital admission and direct ICU admission. We also created logistic regression models to assess associations of individual score components to the outcomes. Results:We studied 6931 patients with mean (SD) age 58 (20) years, and 30 day all-cause mortality rate 7%. Hospital and ICU admission rate was 63% and 16% respectively. Sepsis by SIRS was present in 70% of patients. Only respiratory rate and white blood count of the SIRS criteria were associated with 30-day mortality (OR=2.42 [1.94, 3.03] and 2.06 [1.68, 2.54] respectively, both p Conclusions: In emergency department patients with pneumonia, qSOFA outperformed SIRS in relation to 30-day mortality. Secondary outcomes also showed better performance of qSOFA in hospital and ICU admission compared to SIRS. SOFA performed better than qSOFA and SIRS for all outcomes except ICU admission

Abstract 617: Phenotype as a Basis for Selection of BM-MSC-Derived SMCs for Regenerative Repair of Abdominal Aortic Aneurysms

Abdominal aortic aneurysms (AAA) are a leading cause of death in the elderly with over 150,000 new diagnoses annually in the US. They involve bulging of the abdominal aorta due to chronic proteolytic degradation of the wall structural extracellular matrix (ECM), mainly elastin and collagen. There are currently no established medical management approaches for treating small AAAs and early surgical intervention provides no benefit. AAA growth arrest and regression are also prevented by inherently poor auto regenerative repair of elastic matrix by adult vascular smooth muscle cells (SMCs). We have identified bone marrow mesenchymal stem cell-derived SMCs (BM-SMCs) as superior cell types for regenerative cell therapy due to their high elastogenicity and pro-elastogenic and anti-proteolytic effects on AAA SMCs. In this study we investigated if and how phenotypic coordinates of BM-SMCs on a contractile to synthetic phenotypic continuum impact their above functional benefits. BM-SMC subpopulations were generated under 2% &amp; 10% v/v FBS conditions in presence of transforming growth factor beta-1 (TGFβ), with or without platelet derived growth factor (PDGF-BB) under low &amp; high glucose conditions. Phenotypic coordinates of the BM-SMCs were established by analysis of SMC marker (alpha SM actin (αSMA), SM22, caldesmon, smoothelin, MHC) expression with RT-PCR, western blotting, and immunofluorescence (IF) staining. Elastogenicities of the cell subpopulations were compared by analysis of tropoelastin and matrix elastin synthesis (Fastin assay), crosslinking (ELISA for desmosine), IF, and TEM; contractile properties were compared via a carbachol assay and whole cell patch-clamp for intracellular Ca 2+ /K + activity. Overall, our results indicate that 10% FBS + TGF with/without PDGF express higher contractile markers and higher elastic matrix yield when compared to controls (aortic SMCs and MSCs) and other test cases. Together with ongoing studies that are evaluating pro-elastogenic and anti-proteolytic effects of our generated BM-SMCs on AAA SMCs in non-contact coculture, we believe that the results are promising towards identifying superior elastogenic cell sources for a regenerative cell therapy for AAAs, which we are validating in a rat AAA model. </jats:p

A Rare Case of Takayasu Arteritis Presenting as Pericarditis with Effusion

Takayasu arteritis (TAK) is a rare large-vessel vasculitis that is seen primarily in young females of Asian descent and is infrequently diagnosed in the United States. Pericardial effusion with or without pericarditis as a presenting feature of TAK is rare, with only about five percent of cases of pericarditis attributable to any autoimmune etiology. We present a case of a 22-year-old Caucasian woman who presented with a large, symptomatic pericardial effusion of unclear etiology, who after extensive laboratory workup and imaging to include whole-body positron emission tomography (PET) was diagnosed with TAK. In our patient, the use of whole-body PET showing characteristic hypermetabolism within the aortic arch helped secure our diagnosis while avoiding the need for pericardiocentesis. The patient had rapid symptomatic and radiographic improvement with the use of high-dose oral steroids in addition to colchicine and ibuprofen for her pericarditis and associated pericardial effusion. At follow-up just 1 week after initiation of steroids, only trace effusion was identified on transthoracic echocardiogram

Broad-spectrum antibiotic use and poor outcomes in community-onset pneumonia: a cohort study

QuestionIs broad-spectrum antibiotic use associated with poor outcomes in community-onset pneumonia after adjusting for confounders?MethodsWe performed a retrospective, observational cohort study of 1995 adults with pneumonia admitted from four US hospital emergency departments. We used multivariable regressions to investigate the effect of broad-spectrum antibiotics on 30-day mortality, length of stay, cost and Clostridioides difficile infection (CDI). To address indication bias, we developed a propensity score using multilevel (individual provider) generalised linear mixed models to perform inverse-probability of treatment weighting (IPTW) to estimate the average treatment effect in the treated. We also manually reviewed a sample of mortality cases for antibiotic-associated adverse events.Results39.7% of patients received broad-spectrum antibiotics, but drug-resistant pathogens were recovered in only 3%. Broad-spectrum antibiotics were associated with increased mortality in both the unweighted multivariable model (OR 3.8, 95% CI 2.5–5.9; p&lt;0.001) and IPTW analysis (OR 4.6, 95% CI 2.9–7.5; p&lt;0.001). Broad-spectrum antibiotic use by either analysis was also associated with longer hospital stay, greater cost and increased CDI. Healthcare-associated pneumonia was not associated with mortality independent of broad-spectrum antibiotic use. In manual review we identified antibiotic-associated events in 17.5% of mortality cases.ConclusionBroad-spectrum antibiotics appear to be associated with increased mortality and other poor outcomes in community-onset pneumonia.</jats:sec

Preparation Strategies of the Anti-Mycobacterial Drug Bedaquiline for Intrapulmonary Routes of Administration

Mycobacterium tuberculosis (M.tb) has infected one-quarter of the world&rsquo;s population and led to the deaths of 1.6 million individuals in 2021 according to estimates from the World Health Organization. The rise in prevalence of multidrug-resistant and extensively drug-resistant M.tb strains coupled with insufficient therapies to treat such strains has motivated the development of more effective treatments and/or delivery modalities. Bedaquiline, a diarylquinoline antimycobacterial agent, effectively targets mycobacterial ATP synthase but may lead to systemic complications upon oral delivery. Targeted delivery of bedaquiline to the lungs represents an alternative strategy to harness the sterilizing benefits of the drug against M.tb while mitigating off-target side effects. Two pulmonary delivery modalities were developed herein, including dry powder inhalation and liquid instillation. Despite bedaquiline&rsquo;s poor water solubility, spray drying was performed in predominantly aqueous conditions (&ge;80%) to avoid a closed-loop, inert system. Aerosols of spray-dried bedaquiline with L-leucine excipient outperformed spray-dried bedaquiline alone, demonstrating superior fine particle fraction metrics (~89% of the emitted dose below &lt;5 &micro;m), suitable for inhalation therapies. Furthermore, the use of a 2-hydroxypropyl-&beta;-cyclodextrin excipient allowed a molecular dispersion of bedaquiline in an aqueous solution for liquid instillation. Both delivery modalities were successfully administered to Hartley guinea pigs for pharmacokinetic analysis and were well-tolerated by the animals. Intrapulmonary liquid delivery of bedaquiline led to adequate serum absorption and appropriate peak serum concentrations of the drug. The liquid formulation was superior in systemic uptake compared to the powder formulation. The predominant route via which M.tb bacilli enter the body is aerosol droplets that are deposited onto airway surfaces. For this reason, we believe that further studies should focus on inhalation or intrapulmonary therapies that target the site of entry and primary site of infection for M.tb